The invention relates to the assessment of cardiac performance using ultrasound methods, compositions and devices that interrogate interstitial fluid, particularly methods, compositions and devices that provide for the measurement and monitoring of cardiac performance.
A healthy cardiovascular system results from the proper functioning of a number of organ systems. The respiratory, renal, cardiac and vascular systems all directly or indirectly influence cardiovascular physiology, as well as a number of other organ systems. In addition, a myriad of human medical conditions influences cardiovascular performance. Yet, despite the high prevalence of dysfunctional cardiovascular performance and the inherent interrelationship of the cardiovascular system to other organ systems, accurate and reliable assessments of cardiovascular physiology are not typically based on diagnostic tools that probe the influence of multiple organ systems on cardiovascular performance. More importantly, despite the potentially life threatening nature of dysfunctional cardiovascular performance, current diagnostic tests are either time consuming, expensive to perform, require expensive equipment, expert interpretation, or are limited to specialized hospital or outpatient centers, or all of the above.
Traditional methods of assessing cardiovascular performance have consisted of probing a specific cardiovascular function or a particular organ system such as the heart or vascular system to assess the performance of the cardiovascular system. EKG, for example, provides a non-invasive assessment of cardiac electrophysiology. EKG is, however, hampered since it cannot provide accurate information on cardiac pumping function; specifically, EKG cannot assess parameters such as cardiac output or ejection fraction. Additionally, EKG cannot assess the influence of impaired cardiovascular performance and resultant decrease in cardiac output on other organ systems such as the kidneys.
Cardiac radionuclide imaging and magnetic resonance imaging of the heart can both provide detailed information on cardiac pumping function and can be used to assess parameters such as ejection fraction, ventricular stroke volumes etc. However, similar to EKG, neither cardiac radionuclide imaging nor magnetic resonance imaging can be used to assess the influence of impaired cardiovascular performance on other organ systems such as the kidneys or the liver. Similarly, ultrasonic echocardiography cannot be used assess the influence of impaired cardiovascular performance on other organ systems.
Angiography, specifically coronary angiography, is limited to a morphological assessment of the heart and coronary arteries. However, angiography cannot provide a quantitative assessment of cardiovascular function.
Unfortunately, all of these and other current diagnostic methods are limited to the assessment of performance of a particular organ. Although, the influence of other organs systems can by inferred by the presence of certain clinical markers, many of these techniques focus on a particular organ""s function rather than providing an integral assessment of the function of a number of organs operating in concert.
Consequently, the present inventors have recognized the need, among other things, to provide reliable, quantitative and accurate assessments of cardiovascular performance using devices and methods that assess or monitor the physiological manifestations of multiple organ systems on an easily measured diagnostic feature(s) of human physiology. In addition, the inventors desire to provide methods and devices as described herein to permit cost effective monitoring and accurate measurement of cardiovascular performance of patients in a variety of diverse clinical settings.
TECHNICAL FIELD
BACKGROUND
SUMMARY
BRIEF DESCRIPTION OF FIGURES
DETAILED DESCRIPTION OF THE INVENTION
1.0 ABBREVIATIONS AND DEFINITIONS
2.0 INTRODUCTION
3.0 METHODS AND DEVICES FOR MEASURING CAPILLARY RELATED INTERSTITIAL FLUID
Application Sites
Application to Medical Treatments
Different Types of Monitoring
Calculations and Standards
Empirical Methods for Determining Standards
4.0 METHODS AND DEVICES FOR MEASURING CAPILLARY RELATED EDEMA
Anatomical Regions
Use in Medical Conditions and Treatments
Devices For Testing for Capillary Related Edema Related to Insufficient Cardiovascular Performance
Calculations and Standards
5.0 METHODS AND DEVICES FOR MEASURING VASCULAR PERFORMANCE
6.0 METHODS AND DEVICES FOR EVALUATING CARDIAC PERFORMANCE
7.0 METHODS AND DEVICES FOR MULTISITE MONITORING 80
8.0 ULTRASOUND PROBES FOR IN SITU MEASUREMENTS 83
EXAMPLES
GENERAL MATERIALS AND METHODS
EXAMPLE 1: ULTRASONOGRAPHIC MEASUREMENT OF TISSUE THICKNESS IN AN IN VITRO MODEL OF CAPILLARY RELATED EDEMA
EXAMPLE 2: ULTRASONOGRAPHIC MEASUREMENT OF THICKNESS OF CAPILLARY RELATED EDEMA IN A MODEL OF VENOUS INSUFFICIENCY AND RIGHT VENTRICULAR CARDIAC FAILURE
PUBLICATIONS
U.S. PATENT DOCUMENTS
FOREIGN PATENT DOCUMENTS
OTHER PUBLICATIONS
CLAIMS
ABSTRACT
The present invention recognizes for the first time that ultrasound can be applied to assess cardiovascular performance by measuring or detecting capillary related interstitial fluid. The invention finds particular application for convenient and cost effective measurements in a variety of clinical settings. Previously, it was not recognized that diagnostic ultrasound measurements of capillary related interstitial fluid were possible, or precise. Nor was it recognized that clinically rapid shifts in capillary related interstitial fluid distribution in tissues could be monitored using ultrasound methods or devices and related to cardiovascular performance. The invention includes monitoring cardiovascular performance by interrogating interstitial fluid in a subject using ultrasound wave devices and methods as described herein. Aspects of the invention are directed to continuous or intermittent monitoring, such as cardiovascular performance monitoring in a human.
In one embodiment, the invention includes a method of evaluating cardiovascular performance, comprising: transmitting at least one ultrasound signal to a tissue in a subject in need of cardiovascular performance assessment, recording at least one ultrasound signal from the tissue, and determining a capillary related interstitial layer thickness from a first reflective surface to a second, usually an internal, reflective surface, wherein the capillary related interstitial layer thickness is an assessment of capillary related interstitial fluid. Typically, such a subject will be a human desiring a cardiovascular performance assessment because a clinician wishes to use the invention as a part of a diagnosis or the subject wishes to perform a self assessment of cardiovascular performance.
The inventors were also the first to recognize that ultrasound methods and devices could be applied to the assessment of different aspects of integrated cardiac, vascular, renal or hepatic function. Numerous aspects of the present invention circumvent many of the disadvantages of the current techniques for evaluating dynamic performance of the heart or vascular system.
For example, the present invention provides for a noninvasive assessment of vascular performance that is relatively inexpensive, easily performed by a clinician (not necessarily a physician trained in ultrasound techniques) and can integrate tissue effects into the assessment, especially capillary related tissue effects. Typically, a test of vascular performance, includes two basic steps: reducing or increasing blood flow (or pressure) to a tissue in a subject in need of vascular performance assessment (step (a)), and monitoring an interstitial layer thickness (ILT) of the tissue (step (b)). Monitoring ILT with an ultrasound probe can be before, after or concurrent with reducing or increasing blood flow in step (a).
The invention also provides for the first time methods and devices for multisite monitoring of different anatomical regions either concurrently or at predetermined time intervals for cardiovascular performance. Monitoring anatomical changes during clinically relevant time periods or continuous monitoring provide an important diagnostic tool for detecting short or rapid changes in tissue structure, particularly interstitial layer thickness. In contrast to previous work, the invention is able to measure rapid changes in ILT and monitor ILT from different anatomical regions simultaneously or within short time frames to compare ILTs from different regions.
In one aspect, the invention provides for a method of multisite monitoring of ILT for cardiovascular performance. The method comprises transmitting an ultrasound pulse from a first ultrasound probe to a first anatomical region and transmitting an ultrasound pulse from a second ultrasound probe to a second anatomical region. The method includes recording ultrasound signals from a first ultrasound probe to a first anatomical region and recording ultrasound signals from a second ultrasound probe to a second anatomical region. The method also includes monitoring interstitial layer thickness from a first and second, or more, anatomical regions. Typically, the method is practiced by monitoring from the first anatomical region concurrently with monitoring from the second anatomical region.
Another aspect of the invention includes, a system for monitoring cardiovascular performance, comprising a heart electrical signal detection device, and an ultrasound interstitial layer detection device for monitoring cardiovascular performance. The ultrasound interstitial layer detection device can comprise a predetermined set of probes for monitoring interstitial layers a plurality of anatomical locations. The system can include a computational unit to compare at least one ultrasound signal or data resulting from an ultrasound signal with at least one electrical signal from the heart electrical signal detection device or data resulting from the heart electrical signal detection device. The heart electrical signal detection device can be an EKG. The computational unit may be designed for monitoring and managing signals from the ultrasound probe and the plurality of probes. The computational unit may be design to compare an interstitial layer thickness to an established EKG pattern, or ultrasound signals or interstitial layers with electrical signals from the heart.
The invention also includes a system for monitoring cardiovascular performance, comprising an ultrasound source adapted for detecting an interstitial layer and a blood pressure detector, as well as a blood oxygenation or flow detector or combination thereof. The system can be designed to monitor both blood pressure and interstitial layer thickness over at least five minutes using a computational unit. The system can include a blood flow detector. The system can include a computational unit that compares blood flow (or other blood parameter) and interstitial layer thickness over time.
Another related aspect of the invention includes a multi-probe set that may be used for multi-site monitoring of electrical heart signals using a non-ultrasound probe(s) and an ultrasounds probe adapted for detecting ILT. The set can include an ultrasound system to concurrently process first signals from the first ultrasound probe and second signals from the second ultrasound probe. Systems or sets with more than two probes can also be used. Each probe in the set can be adapted for a particular anatomical region or indication. For example, the anatomical region can be selected from the group consisting of the forehead region, anterior tibia region, foot region, distal radius region, elbow region, presternal region and temporal bone region. Preferably, the ultrasound probe is a micro-transducer adapted for monitoring interstitial layer thickness.